N-(alkylthiophenyl) maleimides

ABSTRACT

Disclosed are N-(alkylthiophenyl)maleimide compounds useful for controlling rice blast on rice plants.

United States Patent [191 Bublitz [4 1 Dec. 10, 1974 N-(ALKYLTHIOPHENYL) MALEIMIDES [75] Inventor: Donald E. Bublitz, Concord,Calif.

[73] Assignee: The Dow Chemical Company,

Midland, Mich.

[22] Filed: Nov. 17, 1972 [21] Appl. No.: 307,608

[52] US. Cl 260/3265 S, 424/274 [51] Int. Cl C07d 27/18 [58] Field ofSearch 260/3265 S, 326.5 FM

Primary ExaminerJoseph A. Narcavage Attorney, Agent, or FirmGary D.Street [5 7] ABSTRACT Disclosed are N-(alkylthiophenyl)maleimidecompounds useful for controlling rice blast on rice plants.

2 Claims, No Drawings BACKGROUND OF THE INVENTION 1. Field of theInvention This invention relates to novel N-(alkylthiophenyl)- maleimidecompounds and to compositions and methods employing such compounds inthe control of rice blast.

2. Description of the Prior Art 7 The present invention is useful in thecontrol and prevention of agricultural plant diseases, particularly inthe control of rice blast (Piricularia oryzae) which is the mosthazardous pest in rice plant. In order to prevent the rice blast,organomercury compounds such as phenyl mercuric acetate and phenylmercuric iodide have been previously employed.

However, organomercury compounds and organometallic compounds in generalare residual and accumulate in the soil of treated fields and in ricehulls and thus pose environmental as well as public health prob lems.

Other non-metallic organo compounds known in the art also sufferdisadvantages which proscribe their use as agricultural fungicides. Themost serious drawback suffered with compounds possessing fungicidalactivity is their phytotoxicity to the host rice plant at desired dosagerates employed. N-(2'-methoxyphenyl)- maleimide (the synthesis of whichis described in Chem. Abstracts 52:9025a; see also US. Pat. No.2,205,588) is an example of such a compound which, while found to beactive against rice blast by the applicant, cannot be safely employeddue to its high phytotoxicity to the host rice plant.

SUMMARY OF THE INVENTION It has now been found in accordance with thepresent invention that particular novel substituted maleimide compoundshaving the formula:

' R I o wherein SR is in the orthoor meta-position; and R is an alkylgroup of from 1 to 6 carbon atoms, both inclu- (xca' wherein (SR),, isin the ortho or meta position;

n is O or 1; m is 0 or 1, with the proviso that the sum of n m is always1;

R is an alkyl group of from 1 to 6 carbon atoms;

and X is oxygen or sulfur.

It is very surprising that the maleimide compounds usable according tothe present invention can be safely employed without injury to the hostplant at dosage rates at which known prior art compounds are phytotoxicto the host plant. The active compounds according to the presentinvention thus constitute a valuable addition to the art.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The term alkyl as used hereinmeans both straight and branched chain radicals containing from 1 to 6carbon atoms, as illustrated by, but not limited to, methyl, ethyl,propyl, isopropyl, butyl, isobutyl, amyl, isoamyl, hexyl or the like.Preferred species of the present invention include those maleimidecompounds of Formula I wherein R is alkyl of l to 3 carbon atoms.Further preferred are the maleimide compounds wherein R is methyl.Especially preferred are the maleimide compounds wherein SR is in theortho position.

The instant maleimide compounds of the present invention are obtained bythe process which comprises reacting maleic anhydride with analkylmercaptoanb line compound in the presence of an inert carrier suchas, for example, ethyl ether, methylene chloride or the like, to producea corresponding alkylmercaptomaleanilic acid intermediate. Theintermediate thus obtained is subsequently dehydrated by conventionalprocedures to produce the desired N-(alkylthiophenyl)maleimide. Thereaction directed to the preparation of the alkylmercaptomaleanilic acidintermediate takes place readily at a temperature of from about 20C. tothe reflux temperature of the reaction mixture, preferably attemperatures of from about 20 to about 50C.

The proportions of the maleic anhydride and alkylmercaptoaniline to beemployed are not critical, some of the desired intermediate being formedupon contacting these reactants in any proportions. However, thereaction consumes the maleic anhydride and alkylmercaptoaniline startingmaterials in equimolar proportions and the use of the starting materialsin about such proportions is preferred.

In carrying out the production of the desired product, the maleicanhydride and alkylmercaptoaniline are contacted together in any orderor fashion. In a convenient procedure, the alkylmercaptoaniline reactantis slowly added portionwise to a solution of maleic anhydride andcarrier medium. The temperature of the re action mixture is thenmaintained within the reaction temperature range for a short period oftime. During the reaction period the alkylmercaptomaleanilic acidintermediate begins to precipitate in the reaction mixture. Followingthe reaction period the reaction mixture can be cooled to insure thatmost of the intermediate is precipitated;

The dehydration of the alkylmercaptomaleanilic acid is accomplished bycontacting the aforesaid intermediate with acetic anhydride and sodiumacetate in the presence of an inert carrier, such as hereinbeforementioned. The resulting reaction mixture is heated at a temperaturefrom -120C. with the production of the desired product. ThedesiredN-(alkylthiophenyl)- maleimide product is isolated by such conventionalprocedures as diluting the dehydration mixture with water in order toprecipitate the desired product, the latter thereafter being collectedby filtration or decantation. in another representative procedure, thereaction mixture can be distilled to remove the low boiling constituentsand obtain the N-(alkylthiophenyl)maleimide product as a residue.This'product can be further purified by such procedures as washing withwater or recrystallization from an organic solvent.

In carrying out the preparation of the compound of the presentinvention, it has been found to be unnecessary' to isolate thealkylmercaptomaleanilic acid intermediate. This intermediate can bedehydrated in the reaction mixture in which it was originally formed bythe addition of acetic anhydride and sodium acetate to the reactionmixture following the production of the desired intermediate and heatingthe reaction mixture to a temperature of from 60 to 120C. The desiredN-(alkylthiophenyl)maleimide product is then separated from the reactionmixture as previously described.

The invention will be further explained in detail with reference to thefollowing examples;

EXAMPLE I A mixture of 2-methylmercaptoaniline (11.7 grams) in 30milliliters (ml) of ethyl ether was added dropwise with stirring to asolution of maleic anhydride (8.26 grams) in 90 ml. of ethyl ether.During the contacting of the reactants and for a period of about 1 hourthereafter, the reaction mixture was heated at the .boiling temperatureand under reflux. Following the heating period, the reaction mixture wascooled. During the reaction the Z-methylthiomaleanilic acid productprecipitated in the reaction mixture as a crystallinesolid. This solidwas removed from the reaction mixture by filtration and dried (meltingpoint 121C).

The 2-methylthiomaleanilic acid (8.6 grams) obtained by filtration wassuspended in a mixture of 2.0

. grams of sodium acetate and 25 ml. of acetic anhydride. The resultingmixture was heated at about 90C. for a period of one-half hour on asteam bath. Following the heating period, the reaction mixture wascooled and thereafter diluted with water. During the dilution, thedesired N-(2-methylthiophenyl)maleimide product precipitated from thediluted reaction mixture and was removed therefrom by filtration. Theproduct was thereafter dried and found to melt at a temperature of8488C. Analysis calculated for C H NO S: C, 60.2; H, 4.1; N, 6.4. Found:C, 60.7; H, 4.6; N, 6.8.

In accordance with the procedures and reactants employed in Example 1above, the replacement of 2-methylmercaptoaniline with:

B-methylthioaniline;

4-methylthioaniline;

2-isopropylthioaniline;

2-n-pentylthioaniline;

3-ethylthioaniline;

3-n-butylthioaniline; and

3-n-hexylthioaniline, yields the following compounds of the presentinvention:

N-( 3 '-methylthiophenyl )maleimide (melting at 54C.

4 N-(4-methylthiophenyl)maleimide (melting atN(2'-isopropylthiophenyl)maleimide (molecular weight 247.2);N-(2-n-pentylthiophenyl)maleimide (molecular weight 275.2); I N-(3'-ethylthiophenyl)maleimide (molecular weight N-( 3-n-butylthiophenyl)maleimide (molecular weight 261.2); and N-( 3 -n-hexylthiophenyl)maleimide (molecular weight 289.2).

The foregoing compounds are suitable for use in the controlof rice blastin the form obtained from the reaction mixture; however, the compoundsmay be further purified by recrystallization or other conventionaltechniques to obtain the highly purified compound if desired.

The reactants employed herein are known materials which are eitherreadily available or which can be prepared according to known oranalogous procedures set forth in the art. The maleimide compound ofFormula II wherein m is 1 and X is oxygen is known in the art; see Chem.Abstracts 50:3420e, wherein the synthesis of such compound is described.The compound is also generically taught in US. Pat. No. 2,205,588.However, there are no literature references to the use ofN-(4'-methoxyphenyl)maleimide as a rice blast control agent.

The maleimide compounds of Formulas (l) and (II) are useful asfungicidal agents in the control of rice blast. For such uses, theunmodified compound can be utilized. However, the present invention alsoembraces the use of such compounds with inert solid or liquidagriculturally acceptable carriers. Thus, for example, a compound can bedispersed on a finely divided solid and employed therein as a dust.Also, the compounds, or a solid composition comprising the compound, canbe-dispersed in water, typically with the aid of a wetting agent, andthe resulting aqueous suspension employed as a spray, drench or wash. Inother procedures, the compound can be employed as a constituent oforganic liquid compositions, oil-in-water and water-in-oil emul sions,or water dispersions, with or without the addition of wetting,dispersing, or emulsifying agents.

It is to be understood, however, that all of the compounds claimed ascompositions containing them may not be equally effective at similarconcentrations. The exact concentration of the toxic compound to beemployed in the treating compositions is not critical and may varyconsiderably provided rice plants are contacted with a rice blastcontrolling amount of the maleimide compound or compounds employed. Theconcentration of the toxicants in liquid compositions generally is fromabout 1.0 to about 50 percent by weight, although concentrations of upto about weight percent are often employed. In dusts or dryformulations, the concentration of the toxicant can be from about 1 .0to about 10 weight percent; however, concentrations upto about 95 weightpercent are often conveniently employed. In compositions to be employedas concentrates, the toxicant can be present in a concentration of from5 to about 98 weight percent.

The compounds of this invention can also be employed in admixture withone another or applied admixed with other chemicals which are used inagronomic and horticultural management and are compatible with thecompounds of this invention. Such chemicals can be, but are notrestricted to, the classes of chemicals commonly known as plantnutrients, fertilizers, insecticides and other fungicides, which are notphytotoxic to the host rice plant.

Each of the compounds of the present invention, the utility of which isnot specifically recited hereinafter, has the ability to inhibit orotherwise control rice blast when applied at dosage levels of from about150 to about 600 or more parts per million by weight.

EXAMPLE 2 Separate aqueous compositions containing N-(2-methylthiophenyl)maleimide and N-(3'-methylthiophenyl)-maleimide, areprepared by mixing 4 parts by weight of the compound, 0.08 part byweight of sorbitan trioleate (Span 85), and 0.02 part of sorbitanmonooleate polyoxyethylene derivative (Tween 80) are dispersed in 40milliliters of acetone to produce a concentrate composition in the formof a waterdispersible liquid containing one of the test compounds as thesole active agent.

EXAMPLE 3 A portion of each of the concentrate compositions prepared inExample 2 is diluted with 20 percent isopropanol to provide liquidcompositions containing from 150 to 600 parts per million by weight ofactive compound. Rice plant seedlings to days old (variety, Caloro) weresprayed with the prepared dispersions; after natural drying, the plantswere inoculated with an inoculum of rice blast spores (Piriculariaoryzae) in 10 percent isopropanol. The inoculated plants were maintainedunder conditions conducive to germination of rice blast spore and growthfor a period of 10 days. After the 10 day period, the plants weremicroscopically examined and the lowest amount of active ingredientshowing 90 percent of prevention of spore germination determined. As aresult of such operations, it was found that both of theN-(2-methylthiophenyl)- maleimide and N-(3-methylthiophenyl)maleimidetest compounds had an LD of 150 parts per million. No phytotoxic effectson the host rice plants were observed at the l50 or 600 part per millionconcentrations employed.

In comparative operations, separate concentrate compositions containingeach of the N-(2'-methoxyphenyl )-maleimide and N-( 3methylphenyl)maleimide art compounds were prepared as in Example 2 anddiluted as above to prepare treating compositions containing from 150 to600 parts per million by weight of the test compound. The preparedcompositions were employed in similar rice blast spore treatingoperations as described above. The examination following the 10 dayperiod indicated that, while the N-(2-methoxyphenyl)maleimide compoundhad an LD or 150 parts per million by weight and theN-(3'-methylphenyl)-maleimide compound had an LD of 600 parts permillion, both compounds were phytotoxic to the host rice plants at theindicated dosage rates.

EXAMPLE 4 EXAMPLE 5 Forty-five parts by weight ofN-(2-methylthiophenyl)maleimide is mixed and ground with 5 parts byweight of Triton-155 to prepare a water-dispersible concentratecomposition containing percent by weight of the maleimide compound.

In a further operation, 25 parts by weight of N-(3'-methylthiophenyl)maleimide and 10 parts by weight of Triton-l 55 and 65parts by weight of xylene are mixed together to prepare an emulsifiableconcentrate composition containing 25 percent by weight of the maleimidecompound.

In a similar manner, 25 parts by weight of N-(2-methylthiophenyl)maleimide and 71 parts of fullers earth, 2 parts ofalkyl aryl sulfonate (Nacconol NR) and 2 parts of a polymerized sodiumsalt of a substituted benzoid alkyl sulfonic acid (Daxad No. 27 aremechanically mixed and ground together to prepare a concentrate in theform of a wettable powder and containing 25 percent by weight of themaleimide compound.

A mixture of 20 parts by weight N-(3'-methylthiophenyl)maleimide, 0.1part of Nacconol NR, 0.l part Daxad No. 27, and parts of water andball-milled together to prepare a water-dispersible liquid concentratecomposition containing 20 parts by weight of the maleimide compound.

The compositions thus prepared can be dispersed in water to prepareaqueous compositions which have very desirable wetting and penetratingproperties and are adapted to distribute effective amounts of thedesired maleimide compound for control of rice blast on rice plants.

All starting materials employed in the preparation of the maleimidecompounds of the present invention are known and are either readilyavailable or can be prepared according to known or analogous proceduresset forth in the prior art.

While this invention has been described and exemplitied in terms of itspreferred embodiments, those skilled in the art will appreciate thatmodifications can be made without departing from the spirit and scope ofthe invention.

I claim: 1. The compound which is N-( 2 -methylthiophenyl )maleimide.

2. The compound which is N-( 3 -methylthiophenyl )maleimide.

1. THE COMPOUND WHICH IS N-(2''-METHYLTHIOPHENYL)MALEIMIDE.
 2. Thecompound which is N-(3''--methylthiophenyl)maleimide.